SARS-CoV-2 peptide–Human Leukocyte Antigen complex (SARS-CoV-2 peptide–HLA complex)

SARS-CoV-2 peptide–Human Leukocyte Antigen (HLA) complexes are molecular structures formed by the association of short viral protein fragments (peptides) with HLA molecules on the surface of host cells. These complexes are critical for the immune system's ability to detect and eliminate cells infected with the SARS-CoV-2 virus. During infection, viral proteins such as Spike (S), Nucleocapsid (N), and Membrane (M) are proteolytically processed into peptides, which are then loaded onto HLA Class I or Class II molecules for presentation to CD8+ or CD4+ T cells, respectively (Saini et al., 2021, Science Immunology). Recognition of these complexes by T-cell receptors (TCRs) is a fundamental step in the cellular immune response against COVID-19 (Huisman et al., 2022, Frontiers in Immunology). In therapeutic development, these complexes serve as highly specific targets for next-generation interventions, including TCR-mimic antibodies and TCR-engineered T-cell (TCR-T) therapies. Unlike traditional antibodies that target surface proteins, these modalities can target internal viral proteins presented as pMHC complexes (He et al., 2021, JCI Insight). However, the high polymorphism of HLA genes means that such therapies are often restricted to patients with specific HLA alleles, such as HLA-A*02:01. A significant challenge in targeting these complexes is ensuring high specificity to avoid cross-reactivity with similar self-peptides found in healthy human tissues, which could lead to autoimmune-like toxicities.

Other names

SARS-CoV-2 pMHCSARS-CoV-2 peptide-MHC complexCOVID-19 peptide-HLA complexSARS-CoV-2 pMHC class ISARS-CoV-2 pMHC class II

Binding of T-cell receptors (TCRs) or TCR-mimic antibodies to the peptide-HLA complex, triggering cytotoxic T-lymphocyte (CTL) mediated lysis of infected cells or cytokine release.